BACKGROUND. Through a shRNA synthetic lethal screen we have identified a number of mRNA splicing factors that are required for the viability of KRAS mutant cancer cells. PURPOSE. In this project we aim to address the following questions: 1) the mechanism by which depletion of mRNA splicing factors causes synthetic lethality with the KRAS oncogene; 2) which cellular mRNAs are differentially spliced in KRAS mutant cells; 3) how the changes in mRNA splicing pattern in KRAS mutant cells affect their viability compared to KRAS wild type cells. SIGNIFICANT MATERIALS AND METHODS. 1) shRNAs that target splicing factors. 2) RNA-seq protocol for quantifying mRNA splicing pattern changes. FY2014 ACCOMPLISHMENT. We have identified a novel mechanism by which the splicing of the KRAS gene is regulated. A manuscript describing our finding has been submitted for publication.